Transmission failure
Philippines president Rodrigo Duterte recently revealed that he has myasthenia gravis, a condition where nerve signals fail to be transmitted to the muscles.
THE phrase “transmission failure” is commonly related to motor vehicles, but what happens when a “transmission failure” occurs in the human body?
Myasthenia gravis is an antibody-mediated disease, caused by a failure of impulse transmission from nerve endings to the muscle, making the muscle weak and easily tired.
The word “myasthenia” itself means “muscular weakness”.
Although there is a lack of recent local data, Japanese and Hong Kong studies have shown that the number of new cases detected are about five per year in a population of one million.
However, a recent Korean study reported that there is an increase in the number of cases of patients with myasthenia gravis, particularly among elderly men.
As mentioned earlier, myasthenia gravis is caused by an “error” in nerve impulse transmission to the muscle.
The “error” is due to the presence of an antibody attacking the acetylcholine receptors located on the surface of the muscle cells.
Acetylcholine is the neurotransmitter used at neuromuscular junctions, i.e. it is used to transmit signals from the nerves to the muscles.
The antibody blocks acetylcholine from acting on its receptors, thus preventing muscle contraction.
Repeatedly-blocked impulses can lead to muscle weakness as the muscles are not being used.
The thymus gland, which is located behind the breastbone, has been linked to the regulation of this antibody.
It has been found to be abnormally large in the majority of young patients with myasthenia gravis, with a tumour called thymoma detected in one out of 10 patients.
The disease can start at any age, but it occurs most frequently at ages 20 to 30 in young women and between the age of 50 and 60 in men.
Not many people know that older people are particularly prone to myasthenia gravis, especially men, and many have been misdiagnosed with various other ailments due to low awareness of this condition and relatively non-specific symptoms.
There are two types of myasthenia gravis: a localised form called ocular myasthenia and a generalised form.
With ocular myasthenia, the disease is limited to the muscles around the eyes and rarely spreads to other muscles after three years.
In the generalised form, the disease can spread to involve muscles around the shoulders and hips, as well as muscles that control speech, swallowing and breathing.
Symptoms and tests
As the initial symptoms involve the face and throat muscles, the most common symptoms that are noticed first are the drooping of either eyelids or double vision. Drooping of the eyelid usually affects one side first, before the other.
If the muscles in the limbs are affected as well, even simple tasks such as combing hair or hanging laundry, will become difficult.
In addition, if it were to spread to the muscles controlling swallowing, patients may find their ability to chew and eat affected.
Speech may also be impaired with the voice becoming slurred, while facial expressions may change and be reduced.
However, the degree of weakness varies among individuals.
Nevertheless, patients often find their symptoms worse after exertion and in the evening.
As the muscle weakness improves with rest, one may find their symptoms fluctuating with both “good times” and “bad times”.
In other words, the symptoms come and go, but typically worsen with continuous activity or usage of the affected muscles.
There are several tests that can help confirm a diagnosis of myasthenia gravis:
● Ice pack test
Your doctor puts a bag of ice on the affected droopy eyelid.
After at least two minutes, your eyelid is checked for any improvement – if there is any, it is considered positive for myasthenia gravis.
● Blood test
One of the easiest ways to diagnose myasthenia gravis is by the detection of the abnormal antibodies, i.e. acetylcholine receptor and muscle-specific kinase antibodies, in the blood.
A positive test, together with fitting symptoms and signs, confirms the diagnosis.
● Neurophysiological testing
This testing includes repetitive nerve stimulation (RNS) and single fibre electromyography (SFEMG).
In RNS, the doctor attaches sticky electrodes on certain parts of the body to record nerve responses.
This is done by producing repetitive small pulses of electricity aimed at detecting any reduction in signal, which can be seen in myasthenia gravis.
An SFEMG test would involve sticking a very small needle around the eyes.
Signals are recorded either by slight contraction of the eyes muscles or by giving small pulses of electricity.
Studies have shown that SFEMG is the most sensitive test in detecting nerve transmission failure, especially in cases where other tests fail to show abnormalities.
● Chest imaging
As myasthenia gravis is associated with an abnormal thymus gland, your doctor would arrange a CT (computed tomography) scan of your chest to detect this.
Symptomatic treatment
There is no cure for myasthenia gravis, but depending on the type, various treatments are available to minimise the symptoms.
They are divided into symptomatic treatment, medication to suppress the immune system and surgery, and include:
● Pyridostigmine
The first medication doctors will usually prescribe is pyridostigmine.
This tablet helps by increasing the availability of acetylcholine to the receptors on the muscle cells.
Common side effects are stomach cramps and diarrhoea, which can be easily treated with anti-spasmodic medications.
● Steroids
If weakness is still limiting your daily function despite taking pyridostigmine, your doctor may suggest steroid tablets such as prednisolone.
Steroid medications reduce the response of the harmful antibodies, hence, improving the muscle fatigue and weakness.
You will be advised to start the steroid tablets at a low dose in the clinic.
Any higher dosage will depend on your body weight.
Once your symptoms are controlled, the steroid medication will be reduced to the lowest effective dose by your doctor.
One has to be aware that the long-term use of steroids may bring about many adverse effects such as weight gain, acne, diabetes, thinning of bones and poor wound healing.
● Immunosuppressants
These are medications that may be prescribed by your doctor to reduce your dependence on steroids and their undesirable side effects.
One of the most commonly used immunosupressants is azathioprine. However, it may take months to work.
Common side effects are abnormal liver test results and reduced cell counts.
● Surgery
If you are found to have a thymoma, you will be strongly advised to have the tumour removed.
It has a high risk of turning aggressive, leading to invasion of the surrounding structures.
Even if the tumour is not present, surgery is offered, in particular to young patients with positive acetylcholine antibody levels.
Recent studies have shown that surgery has definite long-term benefits in symptom control.
Thymus surgery can be performed via open surgery or keyhole surgery.
Open surgery involves splitting the breastbone to remove the thymus.
The keyhole method, on the other hand, involves a few small incisions made in the neck and chest, so that a small camera and instruments can be passed through to remove the gland.
Your surgeon may also give you immunoglobulin prior to the surgery to prevent any worsening of your myasthenic symptoms.
When your symptoms severely affect your swallowing and breathing, you are in myasthenic crisis, meaning that you need immediate attention and treatment.
Certain conditions such as stress, surgery, infection and rapid change in treatment regime may tip your previously well-controlled myasthenic symptoms into crisis.
Emergency treatment in this situation involves giving intravenous immunoglobulin (IV Ig) or plasma exchange.
IV Ig is extracted from donated blood and is able to alter undesirable immune responses.
Plasma exchange is a method in which blood is filtered through an external machine to remove harmful antibodies.
The exchange would require a catheter to be inserted in the large vein in the neck or the groin.
Lifestyle changes
Some of the lifestyle changes patients can make to alleviate their condition include:
● Sleep well, eat well
I encourage my patients to have regular meals, a balanced diet, and more importantly, adequate sleep.
Many patients also find relaxation therapy like tai chi and mindfulness exercises helpful.
● Inform doctors you see of your condition
There are more than 30 drugs that can make myasthenic symptoms worse.
Some of the commonly-used ones are antibiotics such as azithromycin and ciprofloxacin, and high blood pressure (hypertension) medication like beta-blockers.
● Wear sunglasses
Myasthenic symptoms can become worse in warm situations.
If your droopy eyelids are troublesome under the sun, wearing sunglasses may help.
● Plan your pregnancy
Most immunosuppressants are potentially harmful to an unborn child, hence, women with myasthenia gravis need to talk to their doctors and come up with a plan before contemplating pregnancy.
Pyridostigmine and steroids can be used safely in pregnancy.
● Be moderate in activity
Don’t exert yourself too much. Accept that living with myasthenia gravis means that there will be good days and bad days.
You don’t have to completely avoid exercising though.
Just start slow and gradually build up your stamina according to your tolerance. Dr Kok Chin Yong is a consultant neurologist. For more information, email starhealth@thestar.com.my. The information provided is for educational purposes only and should not be considered as medical advice.
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